Association between ambient temperature and genitourinary emergency ambulance dispatches in Japan: A nationwide case-crossover study.

Background: Although the effects of temperature on genitourinary morbidity and mortality have been investigated in several countries, it remains largely unexplored in Japan. We investigated the association between ambient temperature and genitourinary emergency ambulance dispatches (EADs) in Japan and the modifying roles of sex, age, and illness severity. Methods: We conducted a time-stratified case-crossover study with conditional quasi-Poisson regression to estimate the association between mean temperature and genitourinary EADs in all prefectures of Japan between 2015 and 2019. A mixed-effects meta-analysis was used to pool the association at the country level. Subgroup analyses were performed to explore differences in associations stratified by sex, age, and illness severity. Results: We found an increased risk of genitourinary EAD associated with higher temperatures. The cumulative relative risk (RR) at the 99th temperature percentile compared with that at the 1st percentile was 1.74 (95% confidence interval (CI) = [1.60, 1.89]). We observed higher heat-related RRs in males (RR = 1.89; 95% CI = [1.73, 2.07]) than females (RR = 1.56; 95% CI = [1.37, 1.76]), and in the younger (RR = 2.13; 95% CI = [1.86, 2.45]) than elderly (RR = 1.39; 95% CI = [1.22, 1.58]). We found a significant association for those with mild or moderate cases (RR = 1.77; 95% CI = [1.62, 1.93]), but not for severe or life-threatening cases (RR = 1.20; 95% CI = [0.80, 1.82]). Conclusion: Our study revealed heat effects on genitourinary EADs in Japan. Men, youth, and mild-moderate illnesses were particularly vulnerable subgroups. These findings underscore the need for preventative measures aimed at mitigating the impact of temperature on genitourinary emergencies.

Cognitive status predicts preoperative instruction compliance.

The most common postoperative complication for older adults is perioperative neurocognitive disorder (PNCD). Its greatest risk factor is preoperative cognitive impairment. Cognitive impairment also predicts higher likelihood of postoperative complications. While the cause of disparity in outcomes is likely multifactorial, the ability to correctly follow perioperative instructions may be one modifiable component. The purpose of this study was to determine whether cognitive impairment led to reduced preoperative instruction compliance and if so, identify barriers and enact a tailored care-plan to close the gap. Our preoperative clinic implemented routine Mini-Cog screening to identify older (age ≥ 65) surgical patients at increased risk. All patients received the same instructions and, on day of surgery, were surveyed to determine correct execution of nil per os guidelines, chlorhexidine wipe use and medication management. Data was stratified by cognitive status to evaluate whether impairment predicted instruction execution. Feedback from patients and families were compiled. Of those who screened negative for impairment, 68% correctly followed instructions, while 84.2% of those impaired struggled with ≥1 instruction(s); impaired patients were more likely to incorrectly follow instructions (OR = 10.5, p-value = 0.001). Areas for change were identified and team-based solutions were enacted with additional support for those with impairment. We found a clear difference in correct execution with respect to cognitive status. By improving instructions as an institution and adding additional support for those with impairment, the compliance gap was significantly reduced. Targeting perioperative instructions and tailoring care in this population may be one modifiable component in the outcome disparity they face.

Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus.

T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such functional reversal reveals that coreceptor proteins promote the helper-lineage fate when encoded by Cd4, but promote the cytotoxic-lineage fate when encoded in Cd8-regardless of the coreceptor proteins each locus encodes. Thus, T cell lineage fate is determined by cis-regulatory elements in coreceptor gene loci and is not determined by the coreceptor proteins they encode, invalidating coreceptor signal strength as the basis of lineage fate determination. Moreover, we consider that evolution selected the particular coreceptor proteins that Cd4 and Cd8 gene loci encode to avoid generating functionally reversed T cells because they fail to promote protective immunity against environmental pathogens.

Visualizing antibody affinity maturation in germinal centers.

Antibodies somatically mutate to attain high affinity in germinal centers (GCs). There, competition between B cell clones and among somatic mutants of each clone drives an increase in average affinity across the population. The extent to which higher-affinity cells eliminating competitors restricts clonal diversity is unknown. By combining multiphoton microscopy and sequencing, we show that tens to hundreds of distinct B cell clones seed each GC and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. Our findings have implications for development of vaccines in which antibodies with nonimmunodominant specificities must be elicited, as is the case for HIV-1 and influenza.